Protection against d-amphetamine toxicity.
The efficacy of diazepam, haloperidol, propranolol, and yohimbine in antagonizing the toxic manifestations of d-amphetamine were studied in rats. In the control group of animals given 75 mg/kg intraperitoneal (ip) d-amphetamine, 95% developed seizures, and 100% died in mean times of 12.6 +/- 1.0 and 50.1 +/- 5.9 minutes, respectively. Significant protection against d-amphetamine-induced death was afforded by pretreatment with haloperidol (1.0 to 20.0 mg/kg) or propranolol (20.0 to 30.0 mg/kg). Diazepam (5.0 to 10.0 mg/kg) significantly reduced the incidence of clinically overt seizures but offered no protection against death. Yohimbine (2.5 to 10.0 mg/kg) was ineffective in preventing either seizures or death. When haloperidol (1.0 mg/kg) was administered in combination with diazepam (2.0 mg/kg), the incidence of death was no different than if haloperidol were given alone. In combination, haloperidol (1.0 mg/kg) and propranolol (10.0 mg/kg) reduced death more than either agent alone. These data support a protective role of haloperidol or propranolol in the treatment of d-amphetamine intoxication and show no protection with diazepam or yohimbine.
Derlet
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Division of Emergency Medicine and Clinical Toxicology, University of California, Davis, School of Medicine.
Albertson
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Rice
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D000818:Animals; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D003975:Diazepam / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy; D013997:Time Factors; D015016:Yohimbine / Q000627:therapeutic use
D015016:Yohimbine; D011433:Propranolol; D006220:Haloperidol; D003975:Diazepam; D003913:Dextroamphetamine